SIRT3多酚激活剂的筛选及其对UVB诱导HaCaT细胞衰老的修复作用

Silent mating type information regulation 2 homolog 3 (SIRT3) is a deacetylase located in the mitochondrial matrix, which plays an important role in mitochondrial energy metabolism, oxidative stress regulation and delaying aging.In this experiment, the SIRT3-EGFP gene report system was constructed and quantitative real-time polymerase chain reaction was performed to screen SIRT3 activators from eight polyphenols including resveratrol, kaempferol, punicalin, punicalagin, fisetin, cafestol, cyanidin 3-glucoside chloride, and delphinidin 3-glucoside chloraid. Moreover, the anti-aging effects of the SIRT3-inducing polyphenols were evaluated in ultraviolet radiation B (UVB)-irradiated HaCaT cells. Our results showed that resveratrol, kaempferol, punicalagin, fisetin and cafestol significantly enhanced the expression of SIRT3 (P < 0.05). Resveratrol, punicalagin, fisetin and cafestol effectively reduced UVB-induced intracellular reactive oxygen species levels. Furthermore, these five polyphenols all significantly increased the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio (P < 0.05), while resveratrol and cafestol, but not the remaining compounds significantly enhanced the superoxide dismutase 2 activity (P < 0.05, P < 0.01). In addition, punicalagin not only activated SIRT3 expression and repaired the cell antioxidant system, but also significantly decreased the activity of SA-β-gal(P < 0.05), a marker of cell senescence. In conclusion, resveratrol, kaempferol, punicalagin, fisetin and cafestol could augment SIRT3 expression. More interestingly, punicalagin significantly repaired UVB-induced cell senescence in HaCaT cells, and the underlying mechanism may be related to the antioxidant pathway of SIRT3-NADPH-GSH/GSSG.